Fibronectin Matrix Formation is a Prerequisite for Colonization of Kidney Tumor Cells in Fibrin.

Fibrin plays an important role in lung metastasis. Here we show that fibrin promotes colony formation in primary kidney tumor cells from patients with kidney metastasis. In addition, we found that inhibition of fibrin formation with the thrombin inhibitor hirudin in nude mice in vivo significantly reduced the metastatic outgrowth of kidney tumor cells.

Transcription elongation factor ELL2 drives Ig secretory-specific mRNA production and the unfolded protein response.

Differentiation of B cells into Ab-secreting cells induces changes in gene transcription, IgH RNA processing, the unfolded protein response (UPR), and cell architecture. The transcription elongation factor eleven nineteen lysine-rich leukemia gene (ELL2) stimulates the processing of the secreted form of the IgH mRNA from the H chain gene. Mice (mus musculus) with the ELL2 gene floxed in either exon 1 or exon 3 were constructed and crossed to CD19-driven cre/CD19(+).

Relocation of CLIC1 promotes tumor cell invasion and colonization of fibrin.

Unlabelled: Chloride intracellular channel 1 (CLIC1) has been shown to be upregulated in various malignancies but its exact function remains unclear. Here, it is revealed that CLIC1 is critical for the stability of invadopodia in endothelial and tumor cells embedded in a 3-dimensional (3D) matrix of fibrin. Invadopodia stability was associated with the capacity of CLIC1 to induce stress fiber and fibronectin matrix formation following its β3 integrin (ITGB3)-mediated recruitment into invadopodia.

Mitotic rate for thin melanomas: should a single mitotic figure warrant a sentinel lymph node biopsy?

Background: The seventh edition of the American Joint Committee on Cancer guidelines recognize mitotic rate (MR) as a component of the staging criteria for cutaneous melanomas with a Breslow depth ≤1 mm.

Objective: This review discusses the evidence behind the threshold of 1 mitosis per square millimeter as a prognostic variable in thin melanomas, particularly because it relates to the decision to pursue a sentinel lymph node biopsy (SLNB).

Materials And Methods: We performed a systematic review using the PubMed database to identify articles that contain prognostic information for thin melanomas based on MR and sentinel lymph node (SLN) status.

Retracted: Guggulsterone inhibits prostate cancer growth via inactivation of Akt regulated by ATP citrate lyase signaling.

We have shown previously that Gugggulsterone (Gug) inhibits growth of cultured LNCaP and PC-3 human prostate cancer cells by causing apoptosis induction in association with reactive-oxygen species (ROS)-dependent activation of c-Jun N-terminal kinase (JNK). The present study builds upon the novel observations and now reveals a novel mechanism of Gug-anticancer activity that ATP citrate lyase (ACLY)-regulated Akt inactivation is involved in Gug-mediated inhibition of prostate cancer growth. Oral gavage of Gug significantly retarded the growth of PC-3 xenografts in athymic mice without causing weight loss and any other side effects.

Invadopodia formation in blood clots: Not so SLUGgish after all.

Blood clotting specifically supports the metastatic dissemination of malignant cells to the lung. We have recently demonstrated that 2 tumor types that are prone to form lung metastases, renal cell carcinoma and soft tissue sarcoma, share specific adhesive mechanisms that support the invasion and colonization of blood clots in the pulmonary vasculature.

Inactivation of ATP citrate lyase by Cucurbitacin B: A bioactive compound from cucumber, inhibits prostate cancer growth.

Prostate cancer, a leading cause of cancer-related deaths in males, is well recognized as having late disease on-set (mostly at age 60-70) and showing slow/latent disease development, and strategies to prevent cancer formation in late manhood may have significant health impacts. Cucurbitacin B (CuB) is a naturally occurring compound that is found abundantly in cucumbers and other vegetables, and it is known to exert anti-cancer activities (primarily via apoptosis-induction) in several human cancers. However, its chemopreventive potential for prostate cancer has not yet been investigated.

Silencing of ETS1 reverses adriamycin resistance in MCF-7/ADR cells via downregulation of MDR1.

Background: Clinical resistance to chemotherapeutic agents is one of the major hindrances in the treatment of human cancers. Erythroblastosis virus E26 oncogene homolog 1 (ETS1) is involved in the drug resistance of various cancer cells, and is overexpressed in drug-resistant human breast cancer cell lines. In this study, we investigated the effects of ETS1 on adriamycin resistance in MCF-7/ADR cells.

Prognostic value of sentinel lymph node biopsy compared with that of Breslow thickness: implications for informed consent in patients with invasive melanoma.

Background: Sentinel lymph node (SLN) status is reportedly a powerful prognosticator of survival. Breslow thickness alone provides significant prognostic information.

Objective: To assess overall survival (OS) according to tumor depth based on SLN status.

Integrin αvβ3 and fibronectin upregulate Slug in cancer cells to promote clot invasion and metastasis.

The blood clotting cascade is selectively involved in lung metastasis, but the reason for this selectivity is unclear. Here, we show that tumor cells that metastasize predominantly to the lung, such as renal cell carcinoma (RCC) and soft tissue sarcoma (STS), have an inherent capacity to generate extensive invadopodia when embedded in a blood clot. Compared with other metastatic cancer cells tested, RCC and STS cells exhibited increased levels of expression of fibronectin and an activated form of the integrin αvβ3, which coordinately supported the generation of an elaborate fibronectin matrix and actin stress fibers in fibrin-embedded tumor cells.

Plasma Fibronectin Promotes Tumor Cell Survival and Invasion through Regulation of Tie2.

Our previous research has shown that plasma fibronectin promotes lung metastasis by facilitating tumor cell invasion in clotted plasma. To evaluate the role of clotted plasma for tumor cell survival, we treated B16F1 cells embedded in a 3-dimensional matrix of fibrin with tumor necrosis factor α (TNFα), a cytokine with anti-tumor activity. Under these conditions, TNFα caused significant cytotoxicity, which was prevented when we added plasma fibronectin to the fibrin clot.

CLT1 targets bladder cancer through integrin α5β1 and CLIC3.

High-grade non-muscle-invasive bladder cancer is commonly treated with Bacillus Calmette-Guérin, an immunotherapeutic that depends on fibronectin and tumor cell integrin α5β1 for internalization into bladder cancer cells. We previously showed that the anti-angiogenic peptide CLT1 forms cytotoxic complexes with fibronectin that are cooperatively internalized into proliferating endothelium through ligation of integrins and chloride intracellular channel 1. While CLT1 has no effect on mature, differentiated cells, we show here that CLT1 is highly cytotoxic for a panel of bladder tumor cell lines as well as a variety of cell lines derived from kidney, lung, breast, and prostate cancer.

A novel esophageal-preserving approach to treat high-grade dysplasia and superficial adenocarcinoma in the presence of chronic gastroesophageal reflux disease.

Background: The optimal treatment strategy of esophageal high-grade dysplasia (HGD) and superficial adenocarcinoma remains controversial.

Methods: Here, we describe endoscopic, circumferential mucosal-submucosal en-bloc resection of the entire abnormal esophageal epithelium with extracellular matrix (ECM) placement to regenerate neoepithelium and minimize stricture. That procedure was then followed by a laparoscopic fundoplication as a novel esophageal-preserving approach to treat HGD and superficial adenocarcinoma in the face of chronic gastroesophageal reflux disease (GERD).

CLT1 targets angiogenic endothelium through CLIC1 and fibronectin.

Angiogenesis is important for tumor growth and metastasis. CLT1 (CGLIIQKNEC), a peptide that binds to tumor interstitial spaces in the presence of fibrin-fibronectin, has structural similarity to the anti-angiogenic β-sheet peptides anastellin and anginex. This similarity is reflected in the ability of CLT1 to form co-aggregates with fibronectin that induce an unfolded protein response and cause autophagic cell death in proliferating endothelial cells.

How much pharyngeal exposure is "normal"? Normative data for laryngopharyngeal reflux events using hypopharyngeal multichannel intraluminal impedance (HMII).

Background: Laryngopharyngeal reflux (LPR) can cause atypical symptoms, asthma, and pulmonary fibrosis. The aim of this study was to establish the normative data for LPR using hypopharyngeal multichannel intraluminal impedance-pH (HMII).

Methods: Asymptomatic subjects underwent endoscopy followed by 24-h HMII using a specialized impedance catheter configured to detect LPR before and after a 2-week course of proton pump inhibitors (PPI).

Fixation of pathological humeral fractures by the cemented plate technique.

Pathological fractures of the humerus are associated with pain, morbidity, loss of function and a diminished quality of life. We report our experience of stabilising these fractures using polymethylmethacrylate and non-locking plates. We undertook a retrospective review over 20 years of patients treated at a tertiary musculoskeletal oncology centre.

Minimally invasive esophagectomy: the evolution and technique of minimally invasive surgery for esophageal cancer.

Beginning with the widespread introduction of laparoscopic cholecystectomy in late 1989, minimally invasive surgical technique has been refined in conjunction with the development of advanced instrumentation and have subsequently been applied to increasingly complicated disease processes. Esophageal surgeons have increasingly incorporated minimally invasive surgery into their practice since the first laparoscopic fundoplication was described by Dallemagne et al. in 1991.

Transoral incisionless fundoplication 2.0 procedure using EsophyX™ for gastroesophageal reflux disease.

Background: Transoral incisionless fundoplication (TIF) using the EsophyX™ system has been introduced as a possible alternative for the treatment of gastroesophageal reflux disease (GERD). The efficacy of this procedure in our centers was evaluated.

Methods: Patients were selected for treatment if they had typical GERD symptoms, failed management with proton pump inhibitors (PPIs), a positive esophageal pH test with symptom correlation, and no hiatus hernia larger than 2 cm.

Plasma fibronectin promotes lung metastasis by contributions to fibrin clots and tumor cell invasion.

The attachment of circulating tumor cells to the blood vessels of distant organs is an important step in metastasis. We show here that experimental lung metastasis by two cell lines, B16F1 melanoma and 3LL lung carcinoma, is greatly reduced in transgenic mice that lack plasma fibronectin. This multifunctional adhesive glycoprotein becomes cross-linked to fibrin during clotting.

Suppressive roles of calreticulin in prostate cancer growth and metastasis.

Calreticulin is an essential, multifunctional Ca(2+)-binding protein that participates in the regulation of intracellular Ca(2+) homeostasis, cell adhesion, and chaperoning. Calreticulin is abundantly expressed and regulated by androgens in prostate epithelial cells. Given the importance of both calreticulin in multiple essential cellular activities and androgens in prostate cancer, we investigated the possibility of a role for calreticulin in prostate cancer progression.

The management of flail chest.

Flail chest is an uncommon consequence of blunt trauma. It usually occurs in the setting of a high-speed motor vehicle crash and can carry a high morbidity and mortality. The outcome of flail chest injury is a function of associated injuries.